REGULATION OF PEPTIDE EXPRESSION IN NEURONAL CELL

描述：这是第二次修订的应用程序， 上级神经递质/神经肽表达的一般问题 颈神经节细胞 基于先前的批评和 根据初步调查结果，申请人现在建议使用 培养的SCG神经元来检验顺行信号 （以PACAP（垂体腺苷酸环化酶激活剂）为代表 多肽）肽）和逆行信号（由CDF/LIF表示 （胆碱能分化因子/白血病抑制因子）） 差异调节的生物合成，内容，mRNA和释放 特异性交感神经递质和神经肽， 受体介导的特异性细胞内信号传导激活 途径。 生物化学，分子和形态学方法将是 用于促进2个具体目标：1）检查PACAP的机制 SCG神经元NPY和儿茶酚胺表达的突触前调节， 研究CDF/LIF对SCG神经递质的调节作用， 神经肽表达和神经表型可塑性。 中的每 这些目标，4个基本问题将得到解决：1）是否有 差异调节特异性神经肽Y和儿茶酚胺？2)是什么 改变表达的细胞基础3)哪些受体 调解行动？4)细胞内信号是什么 受这些因素的影响，？ 这些研究将开始描绘细胞事件，指导 神经递质和肽在发育、应激 损伤和再生。

DESCRIPTION: This is the second revised application addressing the general question of neurotransmitter/neuropeptide expression in superior cervical ganglion cells. Based both on previous criticism and on additional preliminary findings, the applicant now proposes to use cultured SCG neurons to examine the hypothesis that anterograde signals (represented by PACAP (pituitary adenylate cyclase activating polypeptide) peptides) and retrograde signals (represented by CDF/LIF (cholinergic differentiation factor/leukemia inhibitory factor)) differentially regulate the biosynthesis, content, mRNA and release of specific sympathetic neuron transmitters and neuropeptides through receptor-mediated activation of specific intracellular signaling pathways. Biochemical, molecular and morphological approaches will be used to further 2 specific aims: 1) To examine the mechanism of PACAP presynaptic regulation of SCG neuronal NPY and catecholamine expression, and 2) To investigate CDF/LIF regulation of SCG neurotransmitter and neuropeptide expression and neurophenotypic plasticity. For each of these aims, 4 basic questions will be addressed: 1) Is there differential regulation specific for NPY and catecholamines? 2) What is the cellular basis for the altered expression? 3) What receptors are mediating the actions? 4) What are the intracellular signaling mechanisms regulated by these factors? These studies will begin to delineate the cellular events that guide neuronal transmitter and peptide expression in development, stress, injury and regeneration.